Abstract: A series of genes from Salmonella typhimurium are shown to encode products which are implicated in virulence. The identification of these genes therefore allows attenuated microorganisms to be produced. Furthermore, the genes or their encoded products can be used in the manufacture of vaccines for therapeutic application.

Abstract: There is provided vaccine compositions for intranasal administration, which compositions comprise one or more antigens and an effective adjuvant amount of a chitosan.

Abstract: The invention relates to a vaccine comprising a bacterium attenuated by a non-reverting mutation in a gene encoding a protein which promotes folding of extracytoplasmic proteins. Such mutations were initially identified as being useful in vaccines from a bank of randomly inserted, transposon mutants in which attenuation was determined as a reduction in virulence of the organism in the mouse model of infection. Site directed mutation of the gene results in a strain which shows at least 4 logs of attenuation when delivered both orally and intravenously. Animals vaccinated with such a strain are protected against subsequent challenge with the parent wild type strain. Finally, heterologous antigens such as the non-toxic and protective, binding domain from tetanus toxin, fragment C, can be delivered via the mucosal immune system using such strains of bacteria. This results in the induction of a fully protective immune response to subsequent challenge with native tetanus toxin.

Abstract: The invention provides a bacterium attenuated by a non-reverting mutation in each of the aroC gene, the ompF gene and the ompC gene. The bacterium is useful as a vaccine. The bacterium may, for example, be an attenuated strain of E. coli useful in vaccination against diarrhoea.

Abstract: The present invention provides a polypeptide comprising tetanus toxin fragment C, or a fragment thereof, fused to the pre-S1 region of hepatitis B virus (HBV), or a fragment thereof, and/or the pre-S2 region of HBV or a fragment thereof. It also provides vaccine compositions comprising the polypeptide of the invention.

Abstract: The ssaG derived from Salmonella is shown to exert improved expression of heterologous genes compared to other known promoters and therefore can be used advantageously in constructs for the delivery of therapeutic proteins to a patient.

Abstract: The invention provides the use of Hepatitis A virus capsid, or a mucosally immunogenic fragment or epitope thereof, for the manufacture of a mucosal vaccine composition for administration to a mucosal surface of a patient to induce production of serum Immunoglobulin G antibody against Hepatitis A. Preferably the vaccine composition is administered by the intranasal route.

Abstract: The invention provides a DNA molecule comprising a promoter sequence operably linked to a DNA sequence encoding first and second proteins linked by a hinge region wherein in that the promoter sequence can be one having activity which is induced in response to a change in the surrounding environment and the first protein can be Tetanus toxin C fragment or one or more epitopes thereof. The invention also provides intermediate molecules having a promoter operably linked to a DNA sequence encoding a first antigenic sequence and a hinge region, and at or adjacent the 3′-end thereof one or more restriction sites for the introduction of a second anti-genic sequence. In addition, the invention provides replicable expression vectors containing the DNA fusion proteins expressed therefrom, bacterial transformed with the vectors and the use of the bacteria, in vaccines.

Abstract: A series of genes from Salmonella typhimurium are shown to encode products which are implicated in virulence. The identification of these genes threfore allows attenuated microorganisms to be produced. Furthermore, the genes or their encoded products can be used in the manufacture of vaccines for therapeutic application.

Abstract: There is provided vaccine compositions for intranasal administration, which compositions comprise one or more antigens and an effective adjuvant amount of a chitosan.

Abstract: The invention provides the use of Hepatitis A virus capsid, or a mucosally immunogenic fragment or epitope thereof, for the manufacture of a mucosal vaccine composition for administration to a mucosal surface of a patient to induce production of serum Immunoglobulin G antibody against Hepatitis A. Preferably the vaccine composition is administered by the intranasal route.

Abstract: The invention provides a DNA construct comprising a DNA sequence encoding a fusion protein of the formula: TetC-(Z)a-Het, wherein: TetC is the C fragment of tetanus toxin, or a protein comprising the epitopes thereof; Het is a heterologous protein, Z is an amino acid, and a is zero or a positive integer, provided that (Z)a does not include the sequence Gly-Pro. The invention also provides replicable expression vectors containing the constructs, bacteria transformed with the constructs, the fusion proteins per se and vaccine compositions formed from the fusion proteins or attenuated bacteria expressing the fusion proteins.

Abstract: A variety of different types of nasal vaccine systems have been described including cholera toxin, microspheres, nanoparticles, liposomes, attenuated virus, and outer membrane proteins (proteosomes). The present invention is directed toward a novel nasal vaccine composition that utilizes the cationic polysaccharide, chitosan, as a delivery system. Chitosan is a polysaccharide comprising copolymers of glucosamine and N-acetylglucosamine. The term chitosan encompasses a series of chitosan polymers with different molecular weights (50 kDa-2,000 kDa) and degree of acetylation (40%-98%). Several vaccine animal studies were carried out employing influenza or pertussis antigens in combination with chitosan. Nasal administration of chitosan-antigen nasal vaccines induced significant serum IgG responses and secretory IgA levels. Animals vaccinated via the nasal route with various chitosan-antigen vaccines were also found to be protected against the appropriate challenge.

Abstract: The invention provides a vaccine composition in the form of a kit, comprising a first container containing an antigenic preparation comprising influenza antigen or antigens; and a second container containing an effective adjuvant amount of a chitosan which is a deacetylated chitin which is at least 80% deacetylated. The antigenic preparation in the first container preferably comprises haemagglutinin and neuraminidase influenza antigens.

Abstract: The invention provides the use of Hepatitis A virus capsid, or a mucosally immunogenic fragment or epitope thereof, for the manufacture of a mucosal vaccine composition for administration to a mucosal surface of a patient to induce production of serum Immunoglobulin G antibody against Hepatitis A. Preferably the vaccine composition is administered by the intranasal route.

Abstract: The invention relates to a vaccine composition adapted for mucosal administration, and in particular for intranasal administration, the composition comprising an influenza virus antigen or antigens, such as haemagglutinin and neuraminidase influenza virus antigens, and an effective adjuvant amount of a chitosan. The compositions can be used to immunise a host against infection with influenza, the chitosan serving to enhance the stimulation of a protective IgA mucosal immune response and an IgG systemic immune response.

Abstract: Attenuated microorganism for use in immunoprophylaxis in which the attenuation is brought about by the presence of a mutation in the DNA sequence of the microorganism which encodes, or which regulates the expression of DNA encoding a protein that is produced in response to environmental stress, the microorganism optionally being capable of expressing DNA encoding a heterologous antigen.

Abstract: The present invention discloses a novel approach to attenuating bacteria and for their use as live vaccines. The vaccines can be used in human and animal medicine.In particular, there is disclosed a method of attenuating a bacteria by mutating a gene concerned with the regulation of one or more genes concerned with expression of outer membrane proteins, particularly porin proteins.

Abstract: An attenuated microorganism harboring two mutated genes, each of which is located in the organisms aromatic pathway is provided. These organisms can usefully form the basis of a vaccine. They can be genetically engineered so as to express antigens from other pathogens and thus form the basis of a range of multi-valent vaccines.

Abstract: Attenuated microorganism for use in immunoprophylaxis in which the attenuation is brought about by the presence of a mutation in the DNA sequence of the microorganism which encodes, or which regulates the expression of DNA encoding a protein that is produced in response to environmental stress, the microorganism optionally being capable of expressing DNA encoding a heterologous antigen.